15-69416041-C-A

Variant names:

• chr15-69416041-C-A
• rs758710646
• NM_001367805.3:c.59C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367805.3(KIF23):​c.59C>A​(p.Thr20Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T20M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF23 NM_001367805.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

KIF23 (HGNC:6392): (kinesin family member 23) The protein encoded by this gene is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein has been shown to cross-bridge antiparallel microtubules and drive microtubule movement in vitro. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]

KIF23-AS1 (HGNC:27075): (KIF23 and PAQR5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046586096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367805.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF23	NM_001367805.3	MANE Select	c.59C>A	p.Thr20Lys	missense	Exon 2 of 24	NP_001354734.1	A0A7I2V5Y5
	KIF23	NM_138555.4		c.59C>A	p.Thr20Lys	missense	Exon 2 of 23	NP_612565.1	Q02241-1
	KIF23	NM_001367804.2		c.59C>A	p.Thr20Lys	missense	Exon 2 of 22	NP_001354733.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF23	ENST00000679126.1	MANE Select	c.59C>A	p.Thr20Lys	missense	Exon 2 of 24	ENSP00000504770.1	A0A7I2V5Y5
	KIF23	ENST00000260363.9	TSL:1	c.59C>A	p.Thr20Lys	missense	Exon 2 of 23	ENSP00000260363.4	Q02241-1
	KIF23	ENST00000352331.8	TSL:1	c.59C>A	p.Thr20Lys	missense	Exon 2 of 22	ENSP00000304978.6	Q02241-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000458 AC: 1 AN: 218478 AF XY: 0.00000836

Gnomad AFR exome AF: 0.0000673

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423876 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 707926

African (AFR) AF: 0.00 AC: 0 AN: 30924

American (AMR) AF: 0.00 AC: 0 AN: 33718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24860

East Asian (EAS) AF: 0.00 AC: 0 AN: 38274

South Asian (SAS) AF: 0.00 AC: 0 AN: 77788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100760

Other (OTH) AF: 0.00 AC: 0 AN: 58896

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74302

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.21
Sift	Benign	0.58	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.62
MPC		0.31
ClinPred		0.075	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.16
gMVP		0.20
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758710646; hg19: chr15-69708380;